Phosphorus core–shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters

Mengsi Zhan; Dayuan Wang; Lingzhou Zhao; Liang Chen; Zhijun Ouyang; Serge Mignani; Jean-Pierre Majoral; Jinhua Zhao; Guixiang Zhang; Xiangyang Shi; Mingwu Shen

doi:10.1039/D3BM01198D

Phosphorus core–shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters†

Mengsi Zhan,‡^ab Dayuan Wang,‡^b Lingzhou Zhao,‡^c Liang Chen,

^b Zhijun Ouyang,^b Serge Mignani,^d Jean-Pierre Majoral,

^ef Jinhua Zhao,

*^c Guixiang Zhang,*^a Xiangyang Shi

*^bd and Mingwu Shen

*^b

Author affiliations

* Corresponding authors

^a Department of Radiology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China
E-mail: guixiangzhang@sina.com

^b State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China
E-mail: xshi@dhu.edu.cn, mwshen@dhu.edu.cn

^c Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
E-mail: zhaojinhua1963@126.com

^d CQM-Centro de Quimica da Madeira, Universidade da Madeira, Funchal 9020-105, Portugal

^e Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, Toulouse Cedex 4, France

^f Université Toulouse, 118 route de Narbonne, Toulouse Cedex 4, France

Abstract

Nanoplatforms with amplified passive tumor targeting and enhanced protein resistance can evade unnecessary uptake by the reticuloendothelial system and achieve high tumor retention for accurate tumor theranostics. To achieve this goal, we here constructed phosphorus core–shell tecto dendrimers (CSTDs) with a rigid aromatic backbone core as a nanoplatform for enhanced fluorescence and single-photon emission computed tomography (SPECT) dual-mode imaging of tumors. In this study, the phosphorus P-G2.5/G3 CSTDs (G denotes generation) were partially conjugated with tetraazacyclododecane tetraacetic acid (DOTA), cyanine5.5 (Cy5.5) and 1,3-propane sulfonate (1,3-PS) and then labeled with ^99mTc. The formed P-G2.5/G3-DOTA-Cy5.5-PS CSTDs possess good monodispersity with a particle size of 10.1 nm and desired protein resistance and cytocompatibility. Strikingly, compared to the counterpart material G3/G3-DOTA-Cy5.5-PS with both the core and shell components being soft poly(amidoamine) dendrimers, the developed P-G2.5/G3-DOTA-Cy5.5-PS complexes allow for more efficient cellular uptake and more significant penetration in 3-dimensional tumor spheroids in vitro, as well as more significant tumor retention and accumulation for enhanced dual-mode fluorescence and SPECT (after labelling with ^99mTc) tumor imaging in vivo. Our studies suggest that the rigidity of the core for the constructed CSTDs matters in the amplification of the tumor enhanced permeability retention (EPR) effect for improved cancer nanomedicine development.

This article is part of the themed collection: Biomedical Polymer Materials

Biomaterials Science

Phosphorus core–shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters†

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Phosphorus core–shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters

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